星状神经节钙结合蛋白S100A6在心肌梗死后室性心律失常发生中的作用机制研究

星状神经节（SG）激活是心肌梗死（MI）后室性心律失常发生的重要原因。本课题通过蛋白组学等实验证实SG中钙结合蛋白S100A6在MI后含量显著增加，同时MI后SG神经元N型钙通道活性显著增加。细胞实验证实S100A6可增加N型钙通道活性。而动物实验证实，敲低SG中S100A6可降低MI后室性心律失常的发生。但S100A6在MI后室性心律失常中的作用机制并不明确。S100A6可与多种蛋白质发生相互作用，并可调节细胞膜动力学过程。而多种因子可与N型钙通道结合来调节通道特性。由此提出课题假说为SG中S100A6通过与N型钙通道结合影响钙通道动力学特性进而参与MI后室性心律失常的发生。本课题拟从动物和细胞水平上，通过电生理和分子生物学等实验手段阐明MI后SG中S100A6在MI后室性心律失常发生中的作用机制，旨在寻找SG调控MI后室性心律失常发生的新的治疗靶点，具有重要的临床转化价值。

Stellate ganglion (SG) activation is an important cause of ventricular arrhythmia after myocardial infarction (MI). Our proteomic data suggested that the S100A6 expression in SG neurons was significantly increased after MI, and preliminary animal data indicates that the activity of N-type calcium channel was greatly enhanced after MI. In the in vitro experiment, S100A6 could increase the activity of N-type calcium channel. In the in vivo experiment, knockdown of S100A6 in SG can reduce the occurrence of ventricular arrhythmia after MI. However, the mechanism of S100A6 in ventricular arrhythmia after MI remains unclear. S100A6 interacts with a variety of proteins and regulate cell membrane dynamics. Many factors can bind to N-type calcium channel to regulate the channel characteristics. Thus, our hypothesis that the dynamic characteristics of calcium channel is affected by S100A6 in SG through binding to N-type calcium channel, and then participates in the occurrence of ventricular arrhythmia after MI. This project aims to elucidate the mechanism of S100A6 in the occurrence of ventricular arrhythmia after MI through electrophysiological and molecular biological experiments at in vivo and in vitro condition, so as to find a new promising therapeutic target for SG regulation of the occurrence of ventricular arrhythmia after MI, which has important clinical value.